Agency for Research on Cancer has estimated that every year, between two and three million new cases of
non-malignant melanomas and more than 130,000 new cases of melanoma skin cancer are seen world-
wide. Furthermore, as reported by the WHO, melanomas and other skin cancers claimed the lives of
66,000 people in the world (2002).
International response to this threat has been strong. Some 165 countries have agreed to the Montreal
Protocol of 1989, revised in London in 1990, to accelerate the phasing-out of ozone-depleting substances
(ODS): initially chlorofluorocarbons (CFCs), halons and carbon tetrachloride by 2000 and methyl chloro-
form by 2005.^80 As of 2000, industrial production of chlorofluorocarbons has been arrested and atmos-
pheric levels appear to show signs of coming under control.
8.9 Effects of Ionizing Radiation on Nucleic Acids
X-rays, -radiationand high-energy electronsall interact indirectly with nucleic acids in solution as a
result of the formation of hydroxyl radicals, of solvated electrons, or hydrogen atoms from water. In aero-
bic conditions, the most important processes result from HO•radicals, which abstract a hydrogen atom
forming an organic radical which then captures O 2. Measurements of the efficiency of these processes
indicate that for every 1000eV of energy absorbed, about 27 HO•radicals are formed of which 6 react with
the pentoses and 21 react almost randomly with the four bases.^81
8.9.1 Deoxyribose Products in Aerobic Solution
The hydroxyl radical is able to abstract a hydrogen atom from C-4or from any of the other four carbons in
the sugar. The resultant pentose radicals capture oxygen to give a hydroperoxide radicalat C-4or C-5and
this leads directly to cleavage of a phosphate ester bond. Similar reactions at C-1or C-2lead to alkali-
labile phosphate esters that are cleaved on incubation with 0.1M sodium hydroxide at room temperature
in 10min. In both cases, the bases are released intact (Figure 8.35). The use of Fenton’s reagent to gener-
ate hydroxyl radicals is a key component of a DNA footprinting method (Section 5.5.7).
8.9.2 Pyrimidine Base Products in Solution
At least 24 different products have been isolated from -irradiation of thymidine in dilute, aerated solution
and many more are formed in anoxic conditions or in the solid state. Cytosine and the purines show a simi-
lar diversity. The situation is simplified by limiting the study to oxygenated solutions when the principal
site for reaction with the pyrimidines is the 5,6-double bond.^82 Under these conditions, hydroxyhydroper-
oxidesare formed that are semi-stable for thymidine, but break down rapidly for deoxycytidine to give a
range of products, of which the major ones are illustrated (Figure 8.36). About 10% of thymine modifica-
tion occurs at the methyl group with the formation of 5-hydroxymethyldeoxyuridine. Thymine-glycolis
also a significant lesion.
In anaerobic solution, -radiolysis gives 5,6-dihydrothymidine as the major product with a preference
for formation of the 5(R)-stereoisomer.
8.9.3 Purine Base Products
The radiation chemistry of the purines is less well understood than that of the pyrimidines. Deoxyadenosine
can add the HO•radical at C-8 to give either 8-hydroxydeoxyadenosine or, with cleavage of the imidazole
ring, a 5-formamido-4-aminopyrimidine derivative of deoxyribose (Figure 8.37). Guanine has been even
less well studied. However, this situation may change as a result of reports of the formation of 8-hydroxy-
guaninefrom anaerobic irradiation associated, since there is considerable interest in this modified base as
a strongly mutagenic lesion (Section 8.11.2).
322 Chapter 8